Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan.
Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan.
J Diabetes Investig. 2018 Mar;9(2):234-243. doi: 10.1111/jdi.12702. Epub 2017 Jul 29.
The directed differentiation of human pluripotent stem cells, such as embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs), into pancreatic endocrine lineages has been vigorously examined by reproducing the in vivo developmental processes of the pancreas. Recent advances in this research field have enabled the generation from hESCs/iPSCs of functionally mature β-like cells in vitro that show glucose-responsive insulin secretion ability. The therapeutic potentials of hESC/iPSC-derived pancreatic cells have been evaluated using diabetic animal models, and transplantation methods including immunoprotective devices that prevent immune responses from hosts to the implanted pancreatic cells have been investigated towards the development of regenerative therapies against diabetes. These efforts led to the start of a clinical trial that involves the implantation of hESC-derived pancreatic progenitors into type 1 diabetes patients. In addition, patient-derived iPSCs have been generated from diabetes-related disorders towards the creation of novel in vitro disease models and drug discovery, although few reports so far have analyzed the disease mechanisms. Considering recent advances in differentiation methods that generate pancreatic endocrine lineages, we will see the development of novel cell therapies and therapeutic drugs against diabetes based on iPSC technology-based research in the next decade.
人多能干细胞（如胚胎干细胞（hESCs）和诱导多能干细胞（hiPSCs））向胰腺内分泌谱系的定向分化，通过复制胰腺的体内发育过程得到了广泛研究。该研究领域的最新进展使得能够从 hESCs/iPSCs 体外产生具有葡萄糖反应性胰岛素分泌能力的功能成熟的β样细胞。使用糖尿病动物模型评估了 hESC/iPSC 衍生的胰腺细胞的治疗潜力，并研究了包括免疫保护装置在内的移植方法，以防止宿主对植入的胰腺细胞产生免疫反应，从而开发针对糖尿病的再生治疗方法。这些努力导致了一项临床试验的开始，该试验涉及将 hESC 衍生的胰腺祖细胞植入 1 型糖尿病患者体内。此外，已经从与糖尿病相关的疾病中产生了患者来源的 iPSCs，以创建新型体外疾病模型和药物发现，尽管迄今为止很少有报道分析疾病机制。考虑到生成胰腺内分泌谱系的分化方法的最新进展，我们将在未来十年看到基于 iPSC 技术的研究开发针对糖尿病的新型细胞治疗和治疗药物。
